Structural Bioinformatics - Homology modeling & its Scope
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The document discusses homology modeling, a method used to predict protein structures based on homologous sequences with known 3D structures, highlighting its relevance in understanding sequence-structure-function relationships. It outlines practical steps for modeling, including sequence retrieval, template identification, alignment, and quality checks, as well as the need for improvements for proteins with lower similarities. Additionally, it lists various automated web-based tools for homology modeling and mentions job opportunities and research projects related to the field.
Structural Bioinformatics - Homology modeling & its Scope
- 1. HOMOLOGY MODELING Nixon Mendez Department of Bioinformatics
- 2. • Proteins of similar sequences fold into similar structures and perform similar biological functions. • The protein sequence has the intrinsic information to encode the protein structure. Sequence-Structure-Function Relationships
- 3. • Homology modeling also known as comparative modeling uses homologous sequences with known 3D structures for the modelling and prediction of the structure of a target sequence • Homology modeling is one of the most best performing prediction methods that gives “accurate” predicted models. What is Homology Modeling?
- 4. • Retrieving the sequence to be modeled (target sequence) • Identifying suitable templates from PDB using BLAST • Go for the best hit (> 30 - 40% identity) • No need to do modeling if hit is 100% identical to target • Aligning target sequence with template sequences • Remove gapped positions • Remove residues in target that are missing in template • Final alignment should be in PIR format • Performing homology modeling using MODELLER • Change the aligned PIR file to add additional information required by MODELLER • Mind the syntax (most errors occur because of not following the syntax) • Model quality check – WHATIF, PROCHECK, VERIFY3D, ERRAT • Quantitative comparison of model with experimental structure • Assess RMSD using SUPERPOSE Homology modelling practical steps, in brief
- 6. • To model proteins with lower similarities( eg < 30% sequence identity) • To increase accuracy of models and to make it fully automated • Improvements may include simulataneous optimization techniques in side chain modeling and loop modeling • Although comparative modelling needs significant improvement, it is already a mature technique that can be used to address many practical problems Challenges
- 7. • SWISS Model : http://www.expasy.org/swissmod/SWISS-MODEL.html • WHAT IF : http://www.cmbi.kun.nl/swift/servers/ • The CPHModels Server : http://www.cbs.dtu.dk/services/CPHmodels/ • 3D Jigsaw : http://www.bmm.icnet.uk/~3djigsaw/ • SDSC1 : http://cl.sdsc.edu/hm.html • EsyPred3D : http://www.fundp.ac.be/urbm/bioinfo/esypred/ Automated Web-Based Homology Modelling
- 8. • COMPOSER http://www.tripos.com/sciTech/inSilicoDisc/bioInformatics/matchmaker.ht ml • MODELER http://salilab.org/modeler • InsightII http://www.msi.com/ • SYBYL http://www.tripos.com/ Comparative Modeling Server & Program
- 9. SCOPE
- 10. • In Dr. Khaled Barakat’s Lab, Faculty Of Pharmacy, University Of Alberta, Immediate Phd opening and another one in September 2016. Term - 4 year PhD programmes Baylor College of Medicine PhD - Structural and Computational Biology and Molecular Biophysics, MD/PhD Graduate School of Biomedical Sciences Boston University PhD-Bioinformatics, MS Department of Bioinformatics Indiana University at Bloomington MS bioinformatics, PhD School of informatics, Department of Biology Keck Graduate Institute of Applied Life Sciences Professional Masters of Bioscience, PhD Computational and Systems Biology PhD: KGI and the Claremont Graduate University Degrees Department(s)
- 11. • Opportunity: Postdoctoral Fellow (#211314) @ Henry M. Jackson Foundation for the Advancement of Military Medicine -- Bethesda, MD (US) posted on Monday, April 04, 2016 • Opportunity: Bioinformatics Specialist -- Genomics @ Fred Hutchinson Cancer Research Center -- Seattle, WA (US) posted on Thursday, March 31, 2016 • Opportunity: Senior Bioinformatics Engineer -- Python, genomics, cancer @ Dana-Farber Cancer Institute -- Boston, MA (US) posted on Thursday, March 31, 2016 • Opportunity: Postdoctoral Research Fellow in computational and synthetic biology @ University of Edinburgh, UK posted on Monday, March 28, 2016 • Opportunity: Senior Biostatistician, Interdisciplinary Health Sciences Initiative @ University of Illinois at Urbana/Champaign posted on Monday, March 28, 2016 • Opportunity: Postdoctoral Fellow @ Rady Children's Hospital-Institute for Genomic Medicine -- San Diego, CA (US) posted on Wednesday, March 16, 2016 Job opportunity & Post Doctoral
- 12. • Illustrating and homology modeling the proteins of the Zika virus • Structural characterization of human CRTh2: a combined homology modeling, molecular docking and 3D-QSAR-based in silico approach • • Homology modeling and docking studies of ENPP4: a BCG activated tumoricidal macrophage protein • Homology modeling, docking, and molecular dynamics simulation of the receptor GALR2 and its interactions with galanin and a positive allosteric modulator • Optimized method for TAG protein homology modeling: In silico and experimental structural characterization Current Research- 2016
- 13. THANK YOU